PMID- 28260507 OWN - NLM STAT- MEDLINE DCOM- 20180322 LR - 20191210 IS - 1875-5739 (Electronic) IS - 1567-2026 (Print) IS - 1567-2026 (Linking) VI - 14 IP - 2 DP - 2017 TI - Tanshinone IIA Protects Hippocampal Neuronal Cells from Reactive Oxygen Species Through Changes in Autophagy and Activation of Phosphatidylinositol 3-Kinase, Protein Kinas B, and Mechanistic Target of Rapamycin Pathways. PG - 132-140 LID - 10.2174/1567202614666170306105315 [doi] AB - BACKGROUND: Tanshinone IIA is a key active ingredient of danshen, which is derived from the dried root or rhizome of Salviae miltiorrhizae Bge. The tanshinone IIA has protective effects against the focal cerebral ischemic injury. However, the underlying mechanisms remain unclear. METHODS: An in vitro model of cerebral ischemia was established by subjecting cultures of hippocampal neuronal cells to oxygen-glucose deprivation followed by reperfusion (OGD/R). The probes of 5-(and-6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate, acetyl ester (CMH2DCFDA) and 5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine,iodide (JC-1) were used to determine the mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) production. Western-blot was used to detect the expression of proteins in HT-22 cells. RESULTS: The results of cell proliferative assays showed that the tanshinone IIA attenuated OGD/Rmediated neuronal cell death, with the evidence of increased cell viability. In addition, OGD/R exposure led to increase the levels of intracellular reactive oxygen species (ROS), which were significantly suppressed by tanshinone IIA treatment. Furthermore, tanshinone IIA treatment inhibited elevations in MMP and autophagy following exposure to OGD/R. Additionally, OGD/R promoted cell death with concomitant inhibiting phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)/ mammalian target of Rapamycin (mTOR) pathway, which was reversed by tanshinone IIA. CONCLUSION: These results suggest that the tanshinone IIA protects against OGD/R-mediated cell death in HT-22 cells, in part, due to activating PI3K/Akt/mTOR pathway. CI - Copyright(c) Bentham Science Publishers; For any queries, please email at epub@benthamscience.org. FAU - Zhu, Yingchun AU - Zhu Y AD - Department of Neurology Disease, the Affiliated Anhui Provincial Hospital of Anhui Medical University, Hefei 230022, Anhui, China. FAU - Tang, Qiqiang AU - Tang Q AD - Department of Neurology Disease, the Affiliated Anhui Provincial Hospital of Anhui Medical University, Hefei 230022, Anhui, China. FAU - Wang, Guopin AU - Wang G AD - Department of Neurology Disease, the Affiliated Anhui Provincial Hospital of Anhui Medical University, Hefei 230022, Anhui, China. FAU - Han, Ruodong AU - Han R AD - Department of Intensive Care Division, The People's Hospital of Bozhou, Bozhou 236800, Anhui, China. LA - eng PT - Journal Article PL - United Arab Emirates TA - Curr Neurovasc Res JT - Current neurovascular research JID - 101208439 RN - 0 (Abietanes) RN - 0 (Neuroprotective Agents) RN - 0 (Reactive Oxygen Species) RN - 03UUH3J385 (tanshinone) RN - EC 2.7.1.137 (Phosphatidylinositol 3-Kinase) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - W36ZG6FT64 (Sirolimus) SB - IM MH - Abietanes/chemistry/*pharmacology MH - Animals MH - Autophagy/*drug effects MH - Cell Line, Transformed MH - Cell Survival/drug effects MH - Hippocampus/cytology MH - Membrane Potential, Mitochondrial/drug effects MH - Mice MH - Neurons/*drug effects MH - Neuroprotective Agents/chemistry/*pharmacology MH - Phosphatidylinositol 3-Kinase/metabolism MH - Proto-Oncogene Proteins c-akt/metabolism MH - Reactive Oxygen Species/*metabolism MH - Signal Transduction/*drug effects MH - Sirolimus/metabolism PMC - PMC5543574 OTO - NOTNLM OT - Tanshinone IIA OT - cerebral ischemic OT - mitochondrial membrane potential OT - neural cells OT - reactive oxygen species EDAT- 2017/03/07 06:00 MHDA- 2018/03/23 06:00 PMCR- 2017/08/04 CRDT- 2017/03/07 06:00 PHST- 2017/01/24 00:00 [received] PHST- 2017/02/18 00:00 [revised] PHST- 2017/02/20 00:00 [accepted] PHST- 2017/03/07 06:00 [pubmed] PHST- 2018/03/23 06:00 [medline] PHST- 2017/03/07 06:00 [entrez] PHST- 2017/08/04 00:00 [pmc-release] AID - CNR-EPUB-82130 [pii] AID - CNR-14-132 [pii] AID - 10.2174/1567202614666170306105315 [doi] PST - ppublish SO - Curr Neurovasc Res. 2017;14(2):132-140. doi: 10.2174/1567202614666170306105315.